The present invention is concerned with solutions of indolmycin at concentrations at least 2.5% (W/V) for use in the treatment of bacterial infections in mammals, particularly swine.
Indolmycin is a known antibiotic derived by fermentation (see Merck Index, 9th Ed., Monograph No. 4843). Indolmycin was originally designated as PA 155A in U.S. Pat. No. 3,173,923, which generally discloses indolmycin formulations and their use in systemic treatment of bacterial infections, based upon low toxicity in mice and protection of mice from otherwise lethal infections.
The mouse toxicity and protection studies described in the above cited U.S. patent employed suspensions of indolmycin in so-called "Pfizer diluent", essentially the formulation of indolmycin described in Example 8 below, herein designated as formulation #8. Unfortunately, when that standard formulation was later tested for intramuscular toleration in swine, preliminary to an efficacy study, it was determined that swine injected intramuscularly at a dose of 20 mg/kg once daily for two days manifested severe gastrointestinal toxicity, as shown by severe scours, depression, anorexia, weight loss and pathology at necropsy. Even intramuscular injection of only 5 mg/kg once daily for two days resulted in gastrointestinal toxicity as reflected by the resulting scours. Control studies showed that the scours did not result from the vehicle. Indeed, subsequent studies showed that alternative suspensions, e.g., in the di(caprylate/caprate) ester of propylene glycol (formulation #4) or even in water (formulation #7), injected intramuscularly at 5 mg/kg once daily for two days, behaved similarly, or in the case of water, caused even more scours than the standard formulation #8.